[Effects of various compounds on efficacy of artemisinin in a yeast model]

Artemisinin is a key anti-malarial drug and few clinically meaningful resistant cases about its application have so far been reported. The World Health Organization (WHO) officially recommended the use of ACT (Artemisinin-based Combination Therapy) as the first line antimalarial application to increase its inhibitory efficacy and prevent the likely resistance development. Based on our current understanding of artemisinin, a set of compounds were selected to study their interaction with artemisinin by using the yeast (S. cerevisiae) model, in the hope that knowledge gained might provide some references for clinical investigations. In this research, yeast strain (BY4742) was cultured in the nonfermentable YPGE solid medium with 4 μmol · L(-1) artemisinin and one of the selected compounds for 48 hours, and the combined drug efficiency was evaluated by the inhibition of yeast growth. The compounds belong to the categories of oxygenants, antioxidants, metal ions, ion chelators and uncouplers. Among them, 0.2 mmol L(-1) FeCl3, 60 μmol · L(-1) BPS, 1 mmol · L(-1) CuCl2, 0.75 mmol · L(-1) VE and 1 mmol · L(-1) VC antagonized the action of artemisinin, while 40 μmol · L(-1) DNP, 0.1 μmol · L(-1) CCCP and 0.25 mmol · L(-1) H2O2 had synergistic effects. These results suggested that redox-active and mitochondria-dysfunctional compounds could affect artemisinin's potency, supporting our prior proposed mitochondrial model for artemisinin's action. This research in addition provided a convenient method to screen likely artemisinin-interacting compounds.